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(Circulation. 2002;105:270.)
© 2002 American Heart Association, Inc.

Editorials

Reduced Tissue Factor Pathway Inhibitor-1 After Pharmacological Thrombolysis

An Epiphenomenon or Potential Culprit in Rethrombosis?

Prediman K. Shah, MD

From the Division of Cardiology and Atherosclerosis Research Center, Burns and Allen Research Institute and Department of Medicine, Cedars Sinai Medical Center and University of California, Los Angeles, School of Medicine, Los Angeles, Calif.

Correspondence to P.K. Shah, MD, Director, Division of Cardiology and Atherosclerosis Research Center, Cedars Sinai Medical Center, Room 5347, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail shahp@cshs.org

Key Words: Editorials • tissue factor pathway inhibitor • thrombolysis • plasmin

Thrombosis following plaque rupture is the proximate trigger for abrupt coronary artery occlusion and acute coronary syndromes.^1,2 Coronary thrombolysis was reintroduced in the early eighties as a means of recanalizing acutely occluded coronary arteries in evolving myocardial infarction, limiting myocardial damage, preserving ventricular function, and improving clinical outcomes.^3–5 However, it was soon recognized that in addition to the risk of bleeding, thrombolysis failed to achieve robust reperfusion in 25% to 40% of patients, and reocclusion rates of 5% to 15% tended to attenuate the benefits of initial recanalization.^4,6 Several studies demonstrated that pharmacological thrombolysis using plasminogen activators such as streptokinase and tissue type plasminogen activator was followed by a prothrombotic state attributed variously to plasmin-induced platelet activation, exposure of clot-bound thrombin, and the prothrombotic effects of products of plasmin action.⁶ Thus, rethrombosis following thrombolysis was thought to contribute to both resistance to effective thrombolysis and reocclusion following initial recanalization.⁶ These observations provided the rationale for the concurrent use of antiplatelet (aspirin) and antithrombin (heparin) agents with thrombolytic therapy; however, despite their use, thrombolysis failure and rethrombosis/reocclusion rates remained substantial. Failure of aspirin to abolish rethrombosis has been attributed to multiple redundant non-aspirin responsive pathways for platelet activation, and failure of heparin has been attributed to resistance of matrix and clot-bound thrombin exposed after thrombolysis to inhibition by indirect thrombin inhibitors. Thus, other approaches to improving thrombolytic efficacy have included new thrombolytic agents, non-aspirin antiplatelet drugs, and new antithrombins such as low molecular weight heparins, direct thrombin inhibitors, and other anticoagulants.⁷ . . . [Full Text of this Article]

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